The wide prevalence of Waterpipe smoking in today's society has provoked us to study both chemical matrix and toxicological impact of two locally-produced Moâssel products in Egypt “unflavored (KasM) and peach flavored Moȃssel (PFM)". Head space GC-MS analysis allowed the identification of 52 compounds in the volatile profile of both samples with PFM more enriched with oxygenated compounds (72.71%), which made up of 34.23% in KasM profile. Alanine was the major identified compound in KasM (31.96%) versus linalool that was the most abundant constituent (48.16%) in PFM. Several potentially-health hazardous additives and toxic de-novo synthesized substances were also identified. Moreover, KasM and PFM methanol condensates were subjected to metabolomic profiling based on Liquid Chromatography High Resolution Electrospray Ionization Mass Spectrometry (LC-HR-ESI-MS), which showed the presence of a variety of unknown phytochemicals. The smoke obtained by a simulated Waterpipe smoking setup was subjected to pharmacological study using experimental animals to evaluate its toxicological impact on lung tissues. Pulmonary inflammation and increased oxidative stress was evidenced by increased levels of MDA and NOx- as well as histopathological changes in animal lung tissues.